In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an “admission” of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
Systemic hypertension, or high blood pressure, is an extremely common disorder, affecting approximately 30% of adults aged 18 to 74. The vast majority of these cases (approximately 90%) are termed essential, or primary, hypertension due to an unknown etiology. Generally, individuals are diagnosed as having hypertension if they have an abnormally elevated blood pressure (systolic and/or diastolic) upon repeated visits to a clinician. Hypertension tends to increase mortality and shorten the life expectancy of those affected through its effects on major end organs, namely the heart and cardiovascular system, the kidneys, and the brain. Unfortunately, as with many other diseases which do not have outwardly obvious symptoms, only about one-half of those with the disease are aware of the condition.
The circulatory system is a closed system in which the pressure varies constantly. It rises to a peak (termed the systolic pressure) soon after the tightening (contraction) of the main pumping chambers of the heart (the ventricles). It then falls to a lower level (termed the diastolic pressure) just before the next heartbeat/contraction. Thus, the diastolic pressure is the running pressure between heartbeats. In essence, these pressures are determined by the volume of blood being pumped by the heart and the resistance of the peripheral vessels. The total peripheral resistance created by these vessels is, in turn, primarily dependent upon vessel diameter/size which is normally autoregulated to meet the needs of the organism.
Complications secondary to hypertension are numerous and represent many of the health risks associated with this disease. Arterial damage may lead to a decrease in the normal elasticity of these vessels (arteriosclerosis), inhibiting the ability of the arterioles to adjust/adapt to the changing cardiovascular needs of the individual. Persistent elevations in blood pressure also promote atherosclerosis, a narrowing of the arteries resulting from the development of fatty plaques in the intima of larger arteries. This narrowing can decrease the amount of blood flow, inhibiting oxygenation of the tissue. In addition, the increased blood pressure may cause the release of such plaques from the vessel walls leading to the development of occlusions within the circulatory system. These occlusions (or infarcts) cause small areas of hypoxia and cell death. If such occlusions occur in the brain, they may result in a stroke and possibly severe damage. Other common results of prolonged hypertension include cardiac hypertrophy (increased heart size) due to the increased pumping demands placed upon the heart, cardiac failure, renal/kidney failure, and, in extreme instances, blindness due to the rupturing of vessels within the eye.
In clinical medicine, it is common to classify (or stage) hypertension in terms of the pressure at the time of presentation. There are three primary difficulties with this strategy. First, a significant number of hypertensive patients are not reliably detected during the early stages of their disease. Secondly, given individual variability in the progression of hypertension, the severity of the patient's condition cannot be accurately determined based on the stage of hypertension alone. Therefore, the major means of analyzing the severity of the person's disease is to assess the effects of the hypertension on significant end organs (the heart and kidneys); typically through electrocardiograms and blood work. Finally, due to the typical lack of outwardly apparent symptoms of hypertension, individuals are less likely to visit a clinician. This factor becomes even more important among individuals who live in areas or environments, which do not promote regularly schedule health diagnostic visits.
In addition to the heart and kidneys, the eye is a major end organ affected in hypertensive patients. In addition, it is the only place in the body where the rich microvascular networks can be directly observed in a non-invasive manner. Evaluating the changes observed in these arteries and arterioles to discern changes which occur in other end organs and deciphering what immediate/pertinent health risks are present would help speed discovery of this dangerous condition. The present device analyzes and, subsequently, utilizes these changes for diagnostic evaluation.
Our investigations have shown that the ocular vessels change in several distinctive ways secondary to hypertension. We have observed four different grades of retinal vessel damage via an ophthalmoscopic examination:
We characterize the first grade as a generalized arteriolar narrowing. The characteristics comprise a more linear appearance of at least some of the arteries in the retina. We also find that the arteries reflect more light due to wall thickening. Finally, we can see greater variations in artery caliber (size). The second grade is a generalized arteriolar narrowing with focal constrictions. The characteristics comprise arteriovenous (A-V) nipping, e.g., veins may be compressed by crossing arteries. The third grade is an increased arteriolar narrowing, focal constrictions, and/or hemorrhage, and/or exudation with the characteristics further comprising flame shaped hemorrhages and/or soft white (“cotton wool”) exudates (areas of retinal infarction). The forth grade is a further marked arteriolar narrowing, with focal constrictions, hemorrhage, exudation, and/or edema of the disc (papilloedema) and the characteristics further comprising visible swelling of the optic disc and in some cases lipid deposits within the eye.
The choroidal vessels are only viewed directly with difficulty. With the aid of dyes such as fluorescein and indocyanine green, however, they may be more easily functionally visualized. The choroid receives considerable sympathetic innervation. Therefore, vasoconstrictive factors (e.g., angiotensin IT, adrenaline, and vasopressin) and other factors related to sympathetic activity in the cardiovascular system are likely to affect the choroidal system earlier and/or more severely than the retinal vasculature. Using dye tests, one can observe both narrowing of the choroidal vessels and leakage of fluid from these vessels. The areas of leakage often appear to be yellowish in the fundus and are termed Elschnig's spots. A summary is presented below:                Narrowed choroidal vessels detectable using fluorescein        Elschnig's spots are observed following a choroidal infarct as an elongated yellowish spot        Siegrist's spots are observed following an infarct of the retinal pigment epithelium as circular spots along the equator/midline of the eye        Leakage of fluid from the vessels is visible through a variety of dye tests        Subretinal exudates are form by the accumulation of fluid from leakage and may be visualize        Retinal detachment may occur with increased fluid accumulation        Retinal pigment epithelium depigmentation (i.e., death of the retinal pigment epithelium) occurs following chronic focal ischemia        
The optic nerve contains the only true arteries in the eye. The arteries may develop atherosclerosis (vessel wall deposits), which is visible ophthalmoscopically. More commonly, however, one observes optic disc swelling or edema. After chronic edema one observes optic disc pallor and optic disc ischemia. The ischemic changes observed in the optic nerve may actually be secondary to changes in the choroid as much of the nourishment of the optic nerve comes from the choroid. Therefore, changes in the optic nerve often reflect rather late hypertensive changes.
The indirect association of eye findings with hypertension and cardiovascular disease has been established for some time. One may legitimately ask why this association is not exploited more vigorously in clinical medicine to evaluate and assist in classifying hypertensive patients and then directing and monitoring their subsequent therapy. There are at least four basic reasons. First, those physicians who are primarily trained in the care of hypertensive patients have little training in observing the ocular findings. Second, the ocular findings in hypertension are not threatening to vision (except in very advanced/critical need hypertensive patients) and, therefore, are of only moderate interest to physicians interested in treating eye disease. Third, normal clinical evaluation of the ocular signs is difficult. This is due to both normal individual variability and because some of the early changes in hypertension is also observed as the result of the normal aging process. Finally, once hypertension is discovered, simple blood pressure monitoring by well established methods such as a sphygmomanometer can be done routinely with little training.
Prime examples of the difficulties in interpreting ocular findings in hypertension are the changes in the artery size, shape and color. The arteries of normal subjects vary considerably and artery size changes with age. Moreover, the apparent size of the retinal vessels changes with refractive error and intraocular length. Therefore, without an individual adjustment for the eye's optics, absolute size estimates are too variable to be of use in a clinical context. A second example of the difficulty in using ocular display technology in cardiovascular research is the case of cotton wool spots. Cotton wool spots resolve in several months time and if the hypertension is treated, they disappear completely. In many of the places where cotton wool spots were present, however, there are dead ganglion cells, since the cause of the cotton wool spots are the accumulation of axoplasmic materials in hypoxic axons. Due to the lack of blood vessels in the central retina, this loss of visual cells is often unnoticed by the patient and therefore of little or no concern to the ophthalmologist. The pressure of residual nerve fiber layer defects, however, points to a more severe level of end organ damage and can be used as a marker for past periods of hypertension.
A need therefore exists for a non-invasive method for determining hypertension in a patient by obtaining ocular images.